DESCRIPTION (Applicant's Description) The International Registry of Werner Syndrome has existed at the University of Washington for the past 10 years to: 1. ascertain and genotype additional pedigrees from around the world (The Registry is the sole organization in the U.S. that provides genetic confirmation of the WS); 2. establish and cryopreserve cell materials including Epstein-Barr virally transformed peripheral blood B lymphocyte cell lines (LCLs), Primary skin fibroblast cultures, and immortalized skin fibroblast cultures from affected patients and clinically unaffected siblings from these pedigrees; 3. provide fresh peripheral blood samples, cultured cell materials, WRN cDNA, anti-WRN antibodies to colleagues at the University of Washington and elsewhere; and 4.maintain and expand the University of Washington International Registry of Werner Syndrome Database on the Internet as both a security protected Local Area Network for collaborating investigators and as a separate World Wide Web site with public information for clinicians and for a general audience seeking information regarding Werner Syndrome. This proposal would continue these functions with the following enhancements: 1. the establishment of a selection of hTERT immortalized WS and control fibroblasts; 2. sequence analyses of other RecQ helicase genes and other candidate genes in WS patients and in atypical WS cases with no apparent WRN mutations; 3. as a part of the University of Washington Department of Pathology's newly developed net worked computer system we propose to transfer the Registry's local secure intranet functions (clinical and laboratory data) and the public website to a new system with enhanced security, automated backup, and automated viral screens; 4. an expanded effort to analyze and update the clinical data from all pedigrees within the registry; and 5. to make a major effort to obtain large numbers of cryopreserved skin explants and other tissues from autopsied WS subjects to provide additional primary cultures and biochemical assayable materials for investigators here at the University of Washington and at other institutions.